Decreased bone density is caused by aging, nutrition/diet problems such as shortage of calcium intake, lack of exercise, medicines such as adrenal corticosteroids, etc. In particular, women tend to suffer a rapid decrease of bone mass because of decreased estrogen secretion due to menopause. Here, a person having decreased bone density is one whose bone mineral density is 1 SD (Standard Deviation) or more below the young adult mean (>−1 SD), according to the criteria proposed by the WHO research group in 1994; or one whose bone density is 80% or less of the young adult mean (YAM), according to the criteria proposed by the Japanese Society for Bone and Mineral Research in 1996.
Periodontal disease is an infection caused by specific periodontal disease-causing bacteria. Examples of such periodontal disease-causing bacteria include gram-negative anaerobic bacteria such as Porphyromonas gingivalis. Periodontal disease-causing bacteria increase in the plaque that forms around the root of a tooth cervix, inducing chronic inflammation of the surrounding tissues including gingiva, periodontal membrane, and alveolar bone, and thus developing symptoms of periodontal disease. Because of chronic inflammation induced by periodontal disease-causing bacteria, periodontal disease advances resorption of alveolar bone, which supports the teeth, and it is the greatest cause of lost teeth in developed countries.
With respect to postmenopausal women, it has been revealed that there is a correlation between the drop in bone density and the progression of periodontal disease (Yasunari Kurosu et al., Nihon Shika Hozongaku Zassi (The Japanese Journal of Conservative Dentistry), 1998), and decreased bone mass is regarded as a risk factor for periodontal disease.
The finding that a drop in bone density relates to the progression of periodontal disease led to an animal experiment using bisphosphonate, which is a bone resorption inhibitor. It was thus reported that bisphosphonate is useful for inhibiting alveolar bone resorption in experimental periodontitis (Reddy et al., J Periodontol, 66 (3), 211-217, 1995). However, since bisphosphonate has strong side effects, it is not suitable for periodontal disease treatment, which requires long-term medication. Therefore, the development of a pharmaceutical preparation having a high degree of safety has been desired.
Since periodontal tissues do not recover completely even after periodontal disease treatment, the dental root surface of a treated area is exposed. Because inflamed parts and affected tissues are physically removed in the process of treatment, the treated area tends to suffer gingival recession. Accordingly, in a maintenance phase, when the symptoms are stable after periodontal disease treatment, gingival recession and a relapse of periodontal disease are highly likely to occur. Therefore, the development of a pharmaceutical preparation that has a high degree of safety and that is useful for inhibiting gingival recession and maintaining periodontal tissues such as alveolar bone and periodontal membrane is desired.
It is well known that calcium is a necessary nutritional component for growing children, pregnant women, etc. to maintain or enhance the bone calcium density of alveolar bone (“X-ray, optical microscopic, and scanning electron microscopic research on alveolar bone changes due to vitamin D deficiency”, The Journal of the Kyushu Dental Society, 46, 67-88, 1992). Accordingly, there are a large number of calcium food supplements available. It is known that specific calcium salts (such as calcium pantothenate) inhibit alveolar bone resorption, which is related to periodontal disease (Japanese Unexamined Patent Publication No. 1996-133969). It is thus accepted that intake of calcium and calcium salts is effective to some extent in the prevention of periodontal disease.
In contrast, it is known that soy isoflavones abundantly contain components having antibacterial properties and natural bone metabolism improvement actions. Therefore, soy isoflavones have been used together with calcium salts and vitamin D in oral nutritional supplements for osteoporosis prevention and whole-body bone strengthening, and, in the United States of America, they have been sold under the trade names of “Osteo Soy” (FreeLife, U.S.A.) and “Soylife” (Schouten, U.S.A.). Like ordinary calcium supplements, these are in oral tablet, capsule, and powder forms and are not intended for the prevention of periodontal disease. Among soy isoflavones, genistein shows antibacterial activity against periodontal disease-causing bacteria; therefore, it has been used as an antiperiodontitis agent (Japanese Unexamined Patent Publication No. 1992-283518) and has been used together with high-solubility calcium in a food composition for the prevention of periodontal disease or the prevention of periodontal disease progression (Japanese Unexamined Patent Publication No. 1999-243910). However, the above periodontal disease prevention is based on the antibacterial properties of soy isoflavones, and there has been no reported case of inhibited periodontal membrane loss.